Acta Gastroenterológica Latinoamericana ISSN: 0300-9033 [email protected] Sociedad Argentina de Gastroenterología Argentina

De Paula, Juan Andrés; Carmuega, Esteban; Weill, Ricardo Effect of the ingestion of a symbiotic on the bowel habits of women with functional constipation Acta Gastroenterológica Latinoamericana, vol. 38, núm. 1, marzo, 2008, pp. 16-25 Sociedad Argentina de Gastroenterología Buenos Aires, Argentina

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Effect of the ingestion of a symbiotic yogurt on the bowel habits of women with functional constipation Juan Andrés De Paula,1 Esteban Carmuega,2 Ricardo Weill 3

1 Gastroenterology Division - Hospital Italiano of Buenos Aires, Argentina 2 Nutritia 3 Danone Argentina Acta Gastroenterol Latinoam 2008;38:16-25

Summary lue in the basal period, did not experience changes. Background/aims: functional constipation is a preva- Conclusion: the consumption of a symbiotic yogurt by lent problem within the western population. There is women with functional constipation showed a signifi- evidence supporting the fact that the inclusion of pre cant improvement in the parameters related with bowel and in the diet can favorably modify the in- evacuation. The use of this symbiotic food can result in testinal function. The present study evaluates the effect a useful and safe tool for managing constipation. of the consumption of ®, a yogurt containing Key words: Constipation, Probiotics, Prebiotics, 10 8 UFC/g of (DN-173 Intestines, Colon. 010) and fructoligosaccharide, in women between the ages of 18 and 55 with and without functional consti- pation (Rome II criteria). Methods: after a stabiliza- tion and a basal period, women were randomized to re- Efecto de la ingesta de un alimento ceive 2 units/day of Activia or a lacteous dessert without simbiótico sobre el hábito evacuatorio probiotics (control) for a period of 14 days. Afterwards en mujeres con constipación funcional the groups were intercrossed for another 14 days. Resumen Results: of the 399 women who started the study, 378 Introducción/objetivos: la constipación funcional es were eligible for study participation. In the group of wo- un problema prevalente en la población occidental. men with functional constipation (n= 266), the con- Existen evidencias de que la toma de alimentos pre y sumption of the symbiotic was associated with a higher probióticos puede modificar favorablemente el hábito bowel evacuation rate (6.1±2.7 depositions/week with evacuatorio intestinal. En este trabajo se estudió el efec- Activia vs. 5.0±2.6 dep./week in the control group; to de la ingesta de Activia ®, un yogur conteniendo 10 8 P<0.01), an improvement in the quality of the stools UFC/g de Bifidobacterium animalis (DN-173 010) y according to the Bristol scale (3.6±1.0 vs. 3.4±1.0; un fructoligosacárido en mujeres de 18 a 55 años con y P<0.01), a reduced perception of straining effort sin constipación funcional (criterios de Roma II). (1.9±0.8 vs. 2.2±0.9; P<0.01) and a reduced percep- Métodos: luego de sendos períodos de estabilización y tion of pain associated with defecation (0.1±0.2 vs. basal fueron aleatorizadas a recibir durante 14 días 2 0.2±0.3; P<0.01). In the group of women without unidades/día de Activia o de un postre lácteo sin pro- constipation (n=112) there were statistically significant biótico ni prebiótico (control). Luego los grupos fueron variations in equal sense but of smaller magnitude, entrecruzados durante otros 14 días. Resultados: de las with the exception of pain which, having a very low va- 399 mujeres que iniciaron el estudio, 378 fueron eva- luables. En el grupo de constipadas (n= 266) la toma Correspondence: Juan Andrés De Paula del simbiótico se asoció con una mayor frecuencia eva- Servicio de Gastroenterología - Hospital Italiano. Gascón 450, cuatoria (6,1±2,7 dep./semana con Activia vs. (C1181ACH). Ciudad Autónoma de Buenos Aires, Argentina. 5,0±2,6 dep./semana en controles; P<0,01), mejoría Tel: (54-11) 4959-0200 interno 8862 Fax: (54-11) 4959-0200 interno 8294 en la escala de Bristol de calidad de las heces (3,6±1,0 E-mail: [email protected] vs. 3,4±1,0; P<0,01), menor esfuerzo evacuatorio

16 Symbiotic yogurt and functional constipation Juan Andrés De Paula y col

(1,9±0,8 vs. 2,2±0,9; P<0,01) y menor proporción de ders associated with constipation are referred spon- dolor evacuatorio (0,1±0,2 vs. 0,2±0,3 ; P<0,01). En taneously by one third of the people. In recent el grupo sin constipación se observaron variaciones esta- investigations carried out in representative samples dísticamente significativas en igual sentido pero de me- of the argentinean urban population, 27% of the nor magnitud, con excepción del dolor que mostró un respondents spontaneously referred problems rela- valor basal muy bajo. Conclusión: la ingesta del yogurt ted to constipation as being a main motive of pre- prebiótico en mujeres con constipación funcional mos- occupation concerning their health. Of these peo- tró una mejoría significativa de los parámetros relacio- ple, 78% perceived inconveniences associated with nados con la evacuación intestinal. La utilización de constipation at least once a week, 60% of which este alimento simbiótico puede resultar una herramien- reported seeking a solution to this affection throug- ta útil y segura en el manejo de la constipación. hout their diet.6 Palabras claves: Constipación, Probiótico, Prebiótico, There is evidence supporting the fact that the inta- Intestinos, Colon. ke of probiotics can be useful to reduce the affections related with constipation. Three different clinical List of abbreviations: studies,7-9 have demonstrated that the consumption Fructoligosaccharide (FOS) of Activia ®‚ on a daily basis improves colonic transit time and that such effect is dose-dependent. Other Constipation is one of the most prevalent com- studies performed in human volunteers have confir- 10 ® plaints referred by the general population.1 It can be med this benefit. Activia (Danone Argentina) is a secondary to multiple causes, however, in healthy yogurt containing Bifidobacterium animalis DN 8 people it is principally attributed to many of their 173010 (10 colony forming units -CFU- per gram habits that characterize the current lifestyle. The of product) with the natural yogurt starter : abundance of refined foods, the poor intake of die- bulgaris and Streptococcus thermophilus tary fiber or non-digestible residues and physical (10 7 CFU/g of product), with the addition of a small inactivity are probably important factors involved in proportion (0,5 g%) of inulin. Inulin is a fructoligo- the genesis of this disorder. Constipation is more saccharide (FOS) which is obtained from a natural frequent in women, probably due to a hormonal fiber of chicory (chicorium intybus), a polymer of effect,2 many times aggravated during pregnancy 3 fructose containing 1-4 bonds with acti- and/or secondary to the anatomic and functional vity, which stimulates the proliferation of bifidobac- changes in the dynamics of the pelvic floor follo- teria in the intestinal tract.11 The addition of inulin wing delivery. to an exogenous bifidobacteria substantially increa- There is no single definition of constipation. ses the proportion of bifidobacteria in the colonic Most patients define constipation by one or more flora.12 Experimental studies with this combination symptoms: hard stools, infrequent stools (typically called Acti regularis have confirmed that it is capable fewer than three per week), the need for excessive of substantially increasing the concentration of bifi- straining effort, sensation of incomplete bowel eva- dobacteria in both caecum homogenates and colon cuation, an excessive time spent on the toilet or in of mice in vivo, of favorably modifying the produc- unsuccessful defecation.4 The operative definitions tion of organic acids and of decreasing the formation of constipation were built from a combination of of colonic enzymes such as nitroreductase which are parameters; such is the case of the Rome II criteria involved in the transformation of pro-carcinogens used in the current study. into carcinogens.13 In a study published in 1987 in the United States The main objective of this study was to determi- carried out presumptively amongst healthy young ne whether the consumption of Activia, a symbiotic adults, Sandler and Drossman reported a prevalence of yogurt (dairy product) with probiotics and prebio- constipation of 7.3%. Subjects most commonly defi- tics, modifies the principal characteristics and the ned constipation as straining effort and hard stools.5 subjective sensations associated with bowel evacua- Based on the register of the number of depositions tion, evaluated through the stool frequency, stool per week, constipation affects 10% of the popula- shape (Bristol stool scale), straining effort and eva- tion in our country. However, the unspecific disor- cuation pain.

17 Acta Gastroenterológica Latinoamericana – Vol 38 / N° 1 / Marzo 2008

Materials and methods consumed at all times. Participants were instructed With the intention of recruiting almost 300 cons- about being able to abandon the study at any time tipated women and 100 women without constipa- because of their own wish or due to any other unex- tion, 456 six women were invited to participate in pected reason such as intolerance or any other this open, randomized, controlled study in parallel secondary effect. The study was carried out with the groups with intercrossing in the city and outskirts of approval of an independent ethics committee. Buenos Aires from November 2005 through April 2006. The mean age of the participants was 33.5 years, ranging from 18 to 55. All participants pro- Table 1. Main characteristics of Activia® and the ceeded from a routine visit to the nutritionist where desserts used as a Control. they were categorized and invited to participate in Activia® Control Control the study. All participants were categorized accor- yogurt "Ser®" dessert "Serenito®" ding to the Rome II criteria for functional constipa- dessert tion. Those having a BMI > 28, significant chronic 18.1 g 23.1 g 25.3 g pathologies and/or not having had stable dietary Lipids (g) 4.4 g 0.59 g 4.5 g habits for at least the last three months were exclu- Proteins (g) 4.9 5.5 g 3.6 g ded from the study. Patients were also excluded if Calories (kcal) 131 120 kcal 156 kcal they met any of the following criteria: chronic phar- Weight (g)g 125 130 g 110 g macologic treatment that may alter bowel function, dependence on laxatives to complete bowel evacua- tion, catharsis lesser than one time per week and/or the use of manual maneuvers or mechanic means In order to determine the variations in the subjec- (enemas, suppositories) to facilitate bowel move- tive sensation of well-being we used a self percep- ments. tion questionnaire to track symptoms of digestive Determinations were carried out before and after discomfort with a simple questionnaire previously the study in the office visits to the nutritionist. The used by the sponsor (Danone UK) in observational participant’s personal, nutritional and gastrointesti- studies comparing item by item in a direct way,1 nal history was assessed in these meetings. The using a 5 point option multiple choice ("five point determinations carried out in the study included: Likert scale"). The questionnaire was completed at detailed medical history, assessment of detailed the beginning of the study and after concluding the digestive symptoms, a self-reported questionnaire first intervention, allowing a direct comparison bet- based on the perception of the digestive-related qua- ween the subjects that consumed Activia and the lity of life before and after the first intervention, subjects that consumed the control product in an mean consumption per day (by a self- independent manner. filling report regarding the food ingested during the We compared the variations presented before and study), shape of the stools according to the Bristol after the interventions between the two groups for scale, excessive straining effort and pain during each one of the subpopulations. All the emergent bowel evacuation. variables of the population under study (n=378), Participants were randomly assigned to one of the divided into participants with functional constipa- two groups (group 1 and group 2) using a compu- tion (n=266) and participants without functional terized system. Each group received Activia or a constipation (n=112), were studied by the corres- control lacteous dessert (see table 1) respectively ponding method for each type of variable. In order during the first two weeks of the intervention to reduce the residual effect of the previous inter- (interventions A1 and C1 respectively). During the vention, the measurements were done during the following two weeks the interventions were inverted second week of each interventional period. so that group 1 received the control lacteous dessert For variables such as age, fiber consumption and and group 2 received Activia (interventions C2 and defecatory characteristics we used the Wilcoxon sig- A2 respectively). Participants had the number of ned summation test (for paired samples) to compa- rations necessary for each intervention of the study re the Activia® vs. basal intervention, the control vs. delivered to their homes. All the people involved in basal intervention and the Activia® vs. control inter- the investigation knew which product was being vention. To compare group 1 and group 2 (between

18 Symbiotic yogurt and functional constipation Juan Andrés De Paula y col branches) we used the Wilcoxon range summation participants register of consumed food during the test (for two independent samples) and calculated study, shows that constipated women ingested a the odds ratios for an increase in stool frequency, of smaller amount of fiber per day (Table 3); however, at least once a week, and for the improvement in the this difference was not statistically significant. quality of the stools. In order to consider a subject as respondent for a determined variable, we defined the ranges of Table 2. Causes for study drop-outs. abnormal values for each variable after having analyzed the results obtained in the group of Description Nº women without constipation. For variables such as Loss of daily register material 1 frequency, consistency and straining effort we con- Failure to restrict the consumption of probiotics during sidered a value as abnormal if it lay outside a quar- the course of the study 2 tile, either by being beneath the p25 for the varia- Failure to fulfill study registers 3 bles in which a rise was expected, or by being above Medical record not related to the consumption 2 the p75 for those in which a downfall was expected of the product after carrying out the intervention. We have also Unexpected journey during the course of the study 1 calculated the OR for stool frequency using the Voluntary withdrawal from the study 2 current criteria for normality considered as having a Retirement because of mistakes in daily study registers 10 minimum of three bowel movements per week. Total 21 Regarding the pain associated with bowel evacua- tion, subjects were considered abnormal if they had an initial value higher than "zero" (those who have Table 3. Daily ingestion of dietary fiber by women claimed some type of pain). A subject was operati- with and without constipation during the course of vely defined as respondent for a determined variable the study. when such a variable had a value which was consi- dered abnormal before the intervention and normal Constipated Not constipated after the procedure. N 276 118 Dietary fiber consumption 8.7±6.4 9.4±6.5 (g/day) (Media ± SD) Results Of the 456 women who were included in the CI 95% 8.2-9.5 8.2-10.5 analysis, 399 started the study, 57 were excluded for not meeting protocol requirements, 378 being eligi- ble for study participation (266 constipated and 112 not constipated). Regarding the exclusions Regarding the parameters associated with bowel carried out during the course of the study (drop- habits we carried out comparisons between the outs) we found ourselves with two well differentia- interventions A1 and A2 and the interventions C1 ted groups: one corresponding to the participants and C2, not being able to demonstrate significant who had to be excluded because of their own cau- differences, therefore allowing us to unify the results ses, and the other conformed by the subjects that of A1 and A2 and of C1 and C2 under the deno- were excluded because of poor compliance in recor- minations Activia period and Control period, res- ding the characteristics of their bowel habits. The pectively. total number of "dropouts" included 21 partici- In the group of constipated women stool fre- pants, divided in 7 groups (Table 2). Of those par- quency was significantly higher during the Activia ticipants who voluntarily retired from the study, period compared to the one observed during the only two did not give any explanation concerning Control period (6.1±2.7 vs. 5.0±2.6 depositions/ the underlying cause. week respectively: P<0.01). The consumption of The age of the constipated women was 34.9±8.9 Activia was also associated with a significant impro- years (mean and SD), while the age of the women vement in the quality of the stools according to the without constipation was 33.5±8.9 years. Bristol scale (3.6±1.0 vs. 3.4±1.0 respectively; The ingestion of fiber calculated according to the P<0.01). The perception of straining effort was sig-

19 Acta Gastroenterológica Latinoamericana – Vol 38 / N° 1 / Marzo 2008

nificantly reduced during the Activia period compa- Table 4. Effect of the ingestion of the control dessert red to the Control (1.9±0.8 vs. 2.2±0.9 respectively; and Activia on the variables related with intestinal P<0.01). There was also a reduction in the propor- evacuatory function in constipated women. tion of pain associated with bowel evacuation (0.1±0.2 vs. 0.2±0.3 respectively; P<0.01) (Table 4 Constipated women Control Activia p and Figure 1). Bowel movements The differences between the Activia period and per week the Control period are greater when only the Mean ± SD 4.96±2.62 6.09±2.69 <0.0001 constipated women who presented with pain and CI 95% 4.64-5.28 5.76-6.42 straining effort ≥ 3 (moderate to very high) during the basal period are considered in the Stools Shape analysis (Figure 2). Mean ± SD 3.44±1.02 3.61±0.97 <0.003 In the group of women without constipation CI 95% 3.31-3.56 3.49-3.73 there were statistically significant variations in equal sense but of smaller magnitude, with the exception Straining effort of pain, which, having a very low value in the basal Mean ± SD 2.19±0.85 1.94±0.91 <0.0001 period, did not undergo changes (Table 5). CI 95% 2.08-2.30 1.84-2.05 Based on the criteria mentioned above we calcula- ted the odds ratios (OR) between the Activia vs. Pain during bowel evacuation Control interventions for each one of the 4 princi- Mean ± SD <0.0001 pal variables. In Table 6 we can clearly see that the 0.17±0.30 0.08±0.21 CI 95% OR was significantly in favor of Activia compared O.13-0.21 O.06-0.11

Figure 1. Effect of the ingestion of Activia in relation to the control on stool frequency (bowel movements/week), stool shape, pain and straining effort associated with bowel evacuation in constipated women. All constipated women 7

6 Basal Control 5 Activia

4

3

2

1

0 Stool Stool shape Straining Pain frequency effort

20 Symbiotic yogurt and functional constipation Juan Andrés De Paula y col

Figure 2. Effect of the ingestion of Activia in relation to the control regarding stool frequency (bowel movements/week), stool shape, pain and straining effort associated with bowel evacuation in a subgroup of constipated women who presented pain and straining effort during defecation higher or equal to 3 during the basal period. All constipated women 6 Basal 5 Control Activia 4

3

2

1

0 Stool Stool shape Straining Pain frequency effort

Table 5. Effect of the ingestion of the control dessert to the control group for variables such as stool fre- and Activia on the variables related with intestinal quency, straining effort and pain. No difference was evacuatory function in women without constipation. found regarding stool consistency. In relation to the self-reported questionnaire Women without Control Activia p based on the perception of the digestive-related constipation well-being, comparing the differences presented Bowel movements before and after the first intervention in both per week groups, we observed a significant improvement in Mean ± SD 6.67±3.32 7.71±3.60 <0.0001 the constipated population in the matters concer- CI 95% 6.05-7.30 7.03-8.39 ning: the degree of satisfaction with their diges- tion and the perception of uncomfortable sensa- Stool Shape tions resulting from constipation or associated Mean ± SD 3.62±0.84 3.89±0.83 <0.0005 with their low transit. In the population of CI 95% 2.46-3.78 3.73-4.04 women without constipation we observed statisti- cally significant variations in the matters regar- Straining effort ding: discomfort due to excessive flatulence or gas Mean ± SD 1.64±0.62 1.50±0.58 <0.019 retention, discomfort due to abdominal bloating, CI 95% 1.51-1.76 1.38-1.61 sensation of heaviness or lethargy resulting from digestive disorders, discomfort due to digestive Pain during bowel evacuation problems in general, and the importance assigned Mean ± SD 0.06±0.13 0.03±0.13 <0.068 to digestive-related pain or complaints. In the pre- CI 95% O.03-0.10 O.001-0.05 sent study no adverse effects were seen related to either intervention.

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Table 6. Odds ratio (OR) concerning the Activia and Control interventions in the group of constipated women for each one of the principal variables: stool fre- quency and consistency, and effort and pain associated with bowel evacuation.

Criteria of Respondents Respondents response Total Nº with Control with Activia OR IC 95% p Stool frequency > 5/week 177 66 109 2.70 1.75-4.14 <0,001 Stool frequency > 3/week 76 68 48 4.60 1.75-4.14 <0,001 Stool Shape 54 62 62 1.42 0.79-2.54 <0,238 Straining effort 132 96 87 2.18 1.33-3.59 <0,002 Pain during bowel evacuation 98 48 67 2.25 1.26-4.03 <0,006

Discussion rity functional constipation. On the other hand, our This study was performed on young women with presumption was that the inclusion of these two and without functional constipation.21 Constipation groups (severe constipation and alterations in the is most prevalent in women than in men, which we perineum and anorectal area) would have made the believe is a sufficient reason for only including population under study more heterogeneous. women in this study, in this way clearing out an The design of the study 25 consisted in two parallel important variable such as gender. Constipation was and intercrossed branches, each intervention lasting defined according to the Rome II criteria, a valida- two weeks. We must acknowledge the fact that the ted tool widely used in studies for the selection of intercrossing performed two weeks after the first individuals with functional disorders. Although the intervention limited the time of each intervention aim of this study was to evaluate the effect of the and hindered a more prolonged observation. consumption of Activia® in constipated women, a However, on the other hand, the design with inter- group of women without constipation was included crossing enabled all participants to receive both in this work so as to observe the effect of the inter- interventions (Activia and dessert control) which, vention in the population lacking this disorder, compared to a design without crossing-over, dupli- obtaining data which allowed us to clearly define cated the number of individuals who received each the parameters for normality, and making the ope- one of the interventions. The study was carried out rative definitions regarding the women who were in a controlled and open way, using the daily intake respondent for each variable. of two units of a lacteous dessert of the participant’s Women who presented severe constipation or choice as a control (see list I). This implied that referred data suggesting constipation secondary to both the investigators and the participants were alterations in the perineum and anorectal area were fully aware of the interventions performed. The fact deliberately excluded from the study. Although that the participants knew that they were consu- there is not a totally convincing argument denying ming Activia®, a product that is identified by the the possibility that the consumption of Activia may public as being a yogurt which has a regulatory result beneficial for women who present these last effect on the intestinal function, in this way being two conditions, the objective of this work was to able to influence the results observed in this study. asses women who have functional constipation It is known that the effect of placebo can be impor- compatible with a relatively normal life and do not tant, especially in the case of therapies regarding have severe alterations in their intestine’s physio- functional disorders. However, in these circumstan- logy; in other words, healthy women with low seve- ces it is not easy to find an ideal placebo. Such ideal

22 Symbiotic yogurt and functional constipation Juan Andrés De Paula y col placebo should have: 1) organoleptic qualities dies with more prolonged intervention and suspen- undistinguishable from those of Activia®, 2) no sion times (with intake of placebo after the yogurt). identifying label, 3) similar chemical composition A standardized visual scale was used in order to (including modifications made by bacteria in the clinically visualize the changes in stool consistency.14 original ingredients and presence of the bacteria’s Visual scales to evaluate stool consistency or charac- metabolic products), 4) absence of viable bacteria. teristics have been widely used over time.15 It is a This last point is particularly complex. If a product simple, replicable procedure which is directly rela- which is not fermented had been used, that is wit- ted to colonic transit time16-18 measured by other hout bacteria, the products contained in the place- methods such as the use of radiopaque markers. bo would not have been modified by the bacteria, In the group of constipated women we observed a and therefore the presence of viable bacteria not significant increase in stool frequency, a change in being the only variable. Neither is the use of a radia- the aspect of stools (with an upgrade in the Bristol ted (to kill bacteria) an ideal placebo scale), a significant reduction in the perception of because, even though it would contain the products straining effort, and an also significant reduction in of the ingredients modified by the bacteria’s meta- the perception of pain associated with defecation. bolism, it would also contain the components libe- These two last effects are, in our opinion, the most rated by the dead bacteria, which could at the same important changes as they imply a significant reduc- time have some effect on the physiology of the tion in the perception of unpleasant sensations. digestive system. Provided the impossibility to Neither do the increase in stool frequency nor the count with an ideal placebo and with the intention change in stool characteristics necessarily imply a to circumscribe the effects of each one of the prepa- benefit in themselves. However, both variables are rations, it would be necessary to include at least two probably intimately attached to the other two and, placebos: a) a non fermented product and b) a fer- in addition to this having a low cathartic rate is a mented product but containing dead bacteria. This frequent motive of complaint amongst the general resource implies a considerable increase in the num- population. On the other hand, having a high (or ber of subjects to be included in the study. On the daily) evacuation rate has an important value within other hand, the use of new alimentary products also our culture, although not necessarily always associa- implies having to deal with legal matters related to ted with absence of straining effort or pain. The the use of alimentary products which have not been observation that Activia was more active in the sub- approved by official regulatory entities. Based on group of more constipated women indicates that the analysis made, we believe that the decision to probably its benefic effect is not restricted to the carry out this first open study at a national level is mildest constipated women. justified by the operative complexity and high costs Even though this protocol was not designed for of the aforementioned options. These considera- elucidating the mechanisms involved in the effects tions could eventually be taken into account in the observed, there are some considerations which can planning of future studies. be made. The increase in stool frequency could be This study was not designed to evaluate the explained either by an increase in the excreted fecal mechanisms involved in the observed effects. volume or by a reduction in the volume of each However, we can speculate that changes in the intes- deposition. In the present study we have not mea- tinal flora could accelerate the colonic transit, decre- sured fecal volume and therefore we cannot elucida- ase its capacity to reduce the hydrophilia of the te which factor was associated with the increase in intestinal contents, or moderate the capacity of the stool frequency. The upgrade in the Bristol scale colon to absorb water. We also think that it is pos- suggests an increase in stool humectation, that is, sible that this type of interventions, which not only better hydrated feces, and probably a larger total modify the flora in its composition and metabolism fecal volume. On the other hand, as we have already but also modify the neuroendocrine and immune mentioned, there is evidence which demonstrates response of the mucosa and its functional (and per- that the results obtained using the Bristol scale haps structural) consequences, may have to be correlate to colonic transit time measured with observed for a more prolonged period of time in the radiopaque markers19. If we apply this correlation future. Having obtained the results here presented, to the results of our study we can infer that the inta- it would be interesting to plan the realization of stu- ke of Activia could have reduced colonic transit

23 Acta Gastroenterológica Latinoamericana – Vol 38 / N° 1 / Marzo 2008

time in the group of constipated women. The drome could be due to a change in the inflamma- mechanisms involved in the reduction of colonic tory/immunologic response of the mucosa. Recently transit time are not clear. Basically, in the absence of Guyonnet also showed beneficial effects with the significant modifications in the ingestion of ingestion of a probiotic food containing nutrients and fiber (variables that were controlled Bifidobacterium animalis DN-173 010 on discom- during this study), an increase in colonic transit fort HRQoL score and bloating in constipation-pre- velocity could be explained either by a change in dominant IBS, and on stool frequency in subjects intestinal motility, or by an increase in the intra- with <3 stools/week26. colonic volume, or both. Probably both factors The analysis of the results obtained in the group influence each other, making it difficult to establish of women without constipation shows that the inta- which one was primarily modified. The changes in ke of Activia was associated with significant modifi- intestinal motility that could increase transit velo- cations in the same direction but of lesser magnitu- city are: a) an increase in peristaltic contractions, b) de than the ones observed in the constipated group, a reduction in anti-peristaltic contractions, or c) a with the exception of pain, which, having a very low reduction in the tonic contractions of the left colon. score in the basal period, did not experience chan- On the other hand, a primary increase in the intra- ges with the consumption of Activia. colonic volume could be secondary to: a) a larger It is important to emphasize the fact that no volume contributed by the upper gastrointestinal adverse events were seen related to either interven- tract, b) a reduced absorption of the colonic con- tion, showing the high security of the products tent, either because of a change in the under study, both Activia and the desserts used as a secretory/absorptive function of the mucosa or a control. However, in this point we must consider reduced degradation by colonic bacteria (and conse- the fact that one of the exclusion criteria was intole- quent colonic absorption) of osmotic and/or rance to dairy products or yogurt; and therefore this hydrophilic elements, whose absorption depends on may make this conclusion not applicable to the previous endoluminal degradation and c) an increa- general population, especially those having antece- se in the amount of endoluminal bacteria (which dents of intolerance to this type of products. represents approximately 60% of the fecal volume). In conclusion, this prospective, randomized and Our results do not enable us to speculate which of open study shows that the ingestion of Activia can the mechanisms described is or are involved, but it significantly improve the parameters related with is possible that the ingestion of Activia could bowel evacuation in women with functional consti- modify one or more of these factors. pation. The use of this simbiotic can result in a use- It is interesting to point out the fact that a recent ful and safe tool for managing constipation. study shows that the intake of bifidobacterium infantis significantly reduced symptoms in patients with diarrhea-predominant, constipation-predomi- Financial support: nant or alternating diarrhea and constipation irrita- This study was funded in full by Danone Argentina. ble bowel syndrome.20-23 Although the mechanisms involved in the genesis of Acknowledgement: are not entirely known, it is accepted that changes To the associated professionals that have collaborated in gut motility, visceral sensitivity and in immune with the recruitment and handling of the studied po- processes and mood may play an important role in pulation: L Anastasi, A Ballve, L Bergami, C Blanco, this affection. The intake of probiotics may pro- B Bondarzuk, V Bulgell, M Cataldi, V Chamorro, A bably modify the relationship between the intestinal Cohen, P De Rosa, X Echeverría, SM Garcia, C Mo- and the mucosa. The mentioned study rales, V Pasta, D Pizarro, L Pompa, P Qvarnstrom, M shows that the ingestion of bifidobacterium infantis Romero, A Sacks, V San Millan, G Asenzo, L Traut normalized the imbalance of cytokines regulating and M Vernengo. the inflammatory response 24 which is seen in A Pablo Mazzoli por su colaboración técnica. patients with irritable bowel syndrome. For the first time this observation strongly suggests that the Disclosures beneficial effects resulting from the intervention Ricardo Weill is Director of Research and Development with a probiotic in patients with irritable bowel syn- of Danone Argentina and Esteban Carmuega is exter-

24 Symbiotic yogurt and functional constipation Juan Andrés De Paula y col nal scientific advisor of Danone Argentina. 13. Perez Chaia A. Efecto de un principio simbiótico confor- Juan Andrés De Paula has no financial associations mado por Inulina y el Bifidobacterium Animalis DN 173 with Danone other than in this respect and receive no 010 sobre la microflora intestinal de ratones. In CERELA support other than that directly concerned with the press. conduct of the study. 14. O'Donnell LJ, Virjee J, Heaton KW. Detection of pseudo- diarrhoea by simple clinical assessment of intestinal transit rate. BMJ 1990;300:439-440. References 15. Burnett FL. The intestinal rate and the form of the feces. 1. Qualitative UK Consumer Research; Danone UK. Intern Am J of Roentgenol Rad Ther 1921;10:599-604. comunication available by request. 16. Davies GJ, Crowder M, Reid B, Dickerson JW. Bowel 2. Everhart JE, Go VL, Johannes RS, Fitzsimmons SC, Roth function measurements of individuals with different eating HP, White LR: A longitudinal survey of self-reported bowel patterns. Gut 1986;27:164-169. habits in the United States. Dig Dis Sci 1989;34:1153- 17. Sykes NP. Methods of assessment of bowel function in 1162. patients with advanced cancer. Palliative Medicine 1990;4: 3. Thompson WG, Heaton KW: Functional bowel disorders 287-292. in apparently healthy people Gastroenterology. 1980;9: 18. Sykes NP. Methods of assessment of Bowel function in 283-288. patients with advanced cancer. Palliative Medicine 1990;4: 4. Lembo A, Camillieri M: Chronic constipation. NEJM 287-302. 2003;349:1360-1368. 19. O’Mahony L, McCarhy J, Kelly P, Hurley G, Luo F, Chen 5. Sandler RS, Drossman DA: Bowel habits in young adults K, O’Sullivan GC, Kiely B, Collins K, Shanahan F y not seeking health care. Dig Dis Sci 1987;32:841-845. Quigley EMM: Lactobacillus and Bifidobacterium in irrita- 6. Sendra P. Usos y actitudes en el consumo de alimentos. ble bowel syndrome: symptom responses and relationship to Estudio interno del Departamento de Investigación de cytoquine profiles. Gastroenterology 2005;128:541-551. mercado de Danone Argentina realizado sobre una muestra 20. American Gastroenterological Association Clinical Practice representativa de consumidores y no consumidores de la Committee: AGA technical review on irritable bowel syn- categoría. Danone Argentina; 2003. Available by request. drome. Gastroenterology 2002;123:2108-2131. 7. Marteau P, et al. Bifidobacterium animalis strain DN-173 21. Drossman DA, Corazziari E, Talley NJ, et al: Rome II. The 010 shortens the colonic transit time in healthy women: A functional gastrointestinal disorders. Diagnosis, pathophy- double blind randomised controlled study. Aliment siology and treatment: a multinational consensus. 2nd ed. Pharmacol Ther 2002;16:587-593. McLean, VA: Degnon Associates, 2000. 8. Méance S, et al. A fermented with a Bifidobacterium 22. Thompson WG, Heaton KW, Smyth GT, et al: Irritable probiotic strain DN-173 010 shortened oro-fecal gut tran- bowel syndrome in the general practice: prevalence, cha- sit time in elderly. Microbiol Ecol Health Dis 2001; racteristics, and referral. Gut 2000;46:78-82. 13:217-222. 23. Hungin APS, Whorwell PJ, Tack J, el al: The prevalence, 9. Méance S, et al. Recent advances in the use of functional patterns and impact of the irritable bowel syndrome: an foods: effects of the commercial fermented milk with international survey of 40,000 subjects. Aliment Bifidobacterium animalis strain DN-173 010 and yoghurt Pharmacol Ther 2003;17:643-650. strains on gut transit time in the elderly. Microbiol Ecol 24. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and Health Dis 2003;15:15-22. Bibidocaterium in irritable bowel syndrome: symptom res- 10. Bouvier M, et al. Effects of consumption of a milk fer- ponses and relationship to cytokine profiles. mented by a probiotic Bifidobacterium animalis (strain Gastroenterology 2005;128:541-551. DN-173 010) on colonic transit times in healthy humans. 25. Vedhuyzen Van Zanten SJ, Talley NJ; Bytzer P, et al: Bioscience Microflora 2001;20:43-48. Design of trials for functional gastrointestinal disorders. 11. Roberfroid MB, Van Loo JA, Gibson: GR The bifidogenic Gut 1999;45:1168-1177. nature of chicory inulin and its hydrolysis products. J Nutr 26. Guyonnet D, Chassany O, Ducrotte P, Picard C, Mouret 1998;128:11-19. M, Mercier CH, Matuchansky C: Effect of a fermented 12. Bouhnik Y, Flourie B, Andrieux C, Bisetti N, Briet F, milk containing Bifidobacterium animalis DN-173 010 on Rambaud JC: Effects of Bifidobacterium sp fermented the health-related quality of life and symptoms in irritable milk ingested with or without inulin on colonic bifidobac- bowel syndrome in adults in primary care: a multicentre, teria and enzymatic activities in healthy humans. Eur J Clin randomized, double-blind, controlled trial. Aliment Nutr 1996;50:269-273. Pharmacol Ther 2007;26:475-486.

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